First report of the application of simple molecular complexes as organo-catalysts for Knoevenagel condensation

Abstract

A series of molecular complexes have been designed, synthesized and used as organo-catalysts for the first time for very efficient Knoevenagel condensation. Molecular complexes are thermally stable, easily recyclable, and have a low cost of preparation. The role of acidic protons in molecular complexes in Knoevenagel condensations has been identified as the key factor and helps us to provide useful information about the reaction pathway. The acidic proton of a catalyst enhances the electrophilicity of an aldehyde and accelerates the dehydration process of the reaction at room temperature (RT). An eco-friendly, green synthetic protocol for the Knoevenagel condensation is used to synthesize a series of important cyano group containing synthetic precursors for synthesis of biologically active molecules at RT using a minimum amount of catalyst (∼5 mol%) without the need for chromatographic separation techniques. Detailed mechanistic studies and substituent effects of aromatic aldehydes on the reaction have been investigated. In addition, biologically active 2-amino-4H-chromene derivatives have also been synthesized by the Knoevenagel condensation of salicylic aldehydes with active methylene compounds, followed by intramolecular cyclization (via Michael addition) delivering higher yields within shorter reaction times at RT without any need for chromatographic separation. © The Royal Society of Chemistry 2015.